Pyridine → HCID 23652670, compound

HRID 600219Notes

Reaction equation

HRID 600219 reaction equation
C1(N2CCN(C3N=C(N)C=CN=3)CC2)CCCC1.ClC(OC1C=CC=CC=1)=O.N1C=CC=CC=1.C1([O:41][C:42](=O)[NH:43][C:44]2[CH:49]=[CH:48][N:47]=[C:46]([N:50]3[CH2:55][CH2:54][N:53]([CH:56]4[CH2:60][CH2:59][CH2:58][CH2:57]4)[CH2:52][CH2:51]3)[N:45]=2)C=CC=CC=1.Cl.[F:63][C:64]1([F:70])[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1>C(Cl)Cl.CCN(CC)CC>[CH:56]1([N:53]2[CH2:52][CH2:51][N:50]([C:46]3[N:45]=[C:44]([NH:43][C:42]([N:67]4[CH2:68][CH2:69][C:64]([F:70])([F:63])[CH2:65][CH2:66]4)=[O:41])[CH:49]=[CH:48][N:47]=3)[CH2:55][CH2:54]2)[CH2:60][CH2:59][CH2:58][CH2:57]1

Participants

8

Reactant 5

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 42631890HCID 42631890, compound2×HCID 67269341HCID 67269341, compound

Product 1

HCID 23652670HCID 23652670, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 103 mg (0.42 mmol) 2-(4-cyclopentyl-piperazin-1-yl)-pyrimidin-4-ylamine (intermediate 1), 67 mg (0.428 mmol) phenyl chloroformate (commercially available) and 0.1 g (0.12 mmol) pyridine in 4 mL DCM was shaken for 30 min at room temperature. A fraction of this mixture containing 0.07 mmol of the intermediately built [2-(4-cyclopentyl-piperazin-1-yl)-pyrimidin-4-yl]-carbamic acid phenyl ester was treated with 64.8 mg (0.41 mmol) 4,4-difluoro-piperidine, hydrochloride and 0.05 mL NEt3. The mixture was shaken at room temperature and concentrated. Methanol, DMF and water were added and the mixture was subjected to preparative HPLC purification on reversed phase eluting with a gradient of acetonitrile/water (0.05% triethylamine). The combined product fractions were evaporated to dryness to yield 1.1 mg (5%) of the title compound. MS (m/e): 395.3 (MH+).

Workup

  1. stirringThe mixture was shaken at room temperature
  2. concentrationconcentrated
  3. additionMethanol, DMF and water were added
  4. customthe mixture was subjected to preparative HPLC purification on reversed phase
  5. washeluting with a gradient of acetonitrile/water (0.05% triethylamine)
  6. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a318af83984544dfa2788dce4d9ab6f0
Source dataset
uspto-grants-2011_03
Patent number
US07902184B2

Reaction notes

Loading…